Nerve growth factor (NGF) is a protein which regulates the development of the sympathetic and sensory nervous systems. In mouse, NGF is found in high concentration in the submaxillary gland from which it may be secreted into the saliva, and is also found to be secreted by a large number of other tissue types. The objective of the proposed research is the characterization of the structural and functional relationships of submaxillary gland NGF to the factor produced by other sources. The principal aims of this investigation would be: 1) to determine whether submaxillary gland is the sole source of NGF for the peripheral nervous system, one of several sources, or not a source, and 2) to characterize the structural relationship of submaxillary gland NGF to NGF purified from mouse blood and from mouse L cells grown in vitro. The relationship of NGF to the cosecreted and structurally related proteins, kallikrein and epidermal growth factor will be explored. The general approach to be followed would be: 1) to examine the effect of circulating NGF concentrations, in mouse, of orally administered NGF, of epinephrine-stimulated scretion of NGF from submaxillary gland, and of surgical removal of submaxillary gland, 2) to purify and physically characterize the circulating form of NGF to determine whether it is structurally similar to glandular NGF, and 3) to similarly purify and characterize the NGF secreted by mouse L cell grown in vitro.